Endoscopic resection, by either endoscopic mucosal resection or endoscopic submucosal dissection, is the treatment of choice for small (up to 2cm) Tis, T1a, or superficial T1b disease without evidence of nodal metastases, lymphovascular invasion, or grade 3 histology (poor differentiation). Ablation after endoscopic resection can be considered, especially for T1b tumors . These early-stage tumors are rarely associated with nodal metastases, so lymph node dissection may be omitted . Patients with Tis or T1a disease who receive endoscopic resection appear to have similar overall survival outcomes as those who undergo esophagectomy, at considerably less morbidity [34-36]. Endoscopic resection is also appropriate in T1b patients who are unfit for surgery . While the risk of lymph node metastases is substantially higher in this population, outcomes might not necessarily be worse [24, 36].
Esophagectomy is preferred over endoscopic resection in the definitive management of higher-risk Tis and T1a disease, as well as deeper pT1b lesions (staged after endoscopic resection). It is also recommended for low-risk cT1b and cT2 tumors (<2cm, G1, and N0) .
Traditionally, the esophagectomy was either transhiatal (laparotomy and cervical anastomosis) or transthoracic (most commonly laparotomy and right thoracotomy but variations exist), with meta-analyses showing similar outcomes [37, 38]. Minimally invasive approaches have gained traction more recently with promising results [39-41]. Regardless of the chosen procedure, adequate lymph node dissection is imperative for accurate staging and independently prognostic for survival . An effort should be made to remove at least 15 nodes, although optimal number is still debated [33, 42].
Multimodal therapy is recommended for patients with higher-risk cT1b and cT2 lesions (>2cm or G2+) as well as more locoregionally advanced disease. The preferred treatment for resectable disease is typically preoperative two-agent chemoradiotherapy followed by esophagectomy, a sequence with demonstrated survival benefit over surgery alone .
Patients who are not surgical candidates, including those with cervical esophageal cancer or T4b disease invading the trachea, great vessels, or heart, can be managed with definitive chemoradiotherapy. Two prospective randomized trials suggest that definitive chemoradiotherapy achieve comparable outcomes to preoperative chemoradiotherapy followed by esophagectomy in ESCC, making it tempting to pursue this less morbid treatment for all patients [44, 45]. However, these trials have come under criticism and subsequent retrospective studies found a survival benefit with the addition of surgery . Until further evidence is available, preoperative chemoradiotherapy with esophagectomy remains the standard of care for surgical candidates .
There is evidence supporting the use of preoperative or perioperative chemotherapy over surgery alone in EAC, but comparisons to preoperative chemoradiotherapy have been underpowered [47-50]. In particular, the perioperative FLOT regimen, established for gastric cancer and EAC of the EGJ, has gained traction recently. These strategies are reasonable alternatives in the management of select patients with distal EAC .
Nutrition consultation and placement of a feeding tube should be considered in patients undergoing aggressive multimodality treatment.
Chemotherapy and targeted therapies can help manage symptoms and modestly prolong survival. While systemic therapy is associated with higher toxicity, it does not appear to outweigh symptomatic relief as overall quality of life is not diminished . Extrapolating from reports on gastric cancer, the addition of more chemotherapeutic agents can further extend survival and improve response rate, albeit with greater toxicity . Two-agent chemotherapy is considered first line for most patients with esophageal cancer but three-agent chemotherapy may be appropriate in select medically fit patients with good performance status. The combination of a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine) and a platinum agent (e.g., cisplatin or oxaliplatin) is currently considered first line .
The addition of targeted therapies to chemotherapy has produced encouraging results in select patient populations [53-55]. Health Canada and the FDA have approved trastuzumab and ramucirumab for HER2-overexpressing and chemotherapy-refractory patients with GEJ adenocarcinoma, respectively. Other targeted therapies are also showing promising early results, including pembrolizumab which received early FDA approval for select MSI-H/dMMR EGJ adenocarcinoma .
There is emerging evidence for aggressive management of oligometastatic esophageal cancer with resection or radiotherapy directed at the primary tumor or oligometastases [56-62]. Among possible oligometastatic sites, lung and liver metastasectomy have the most supporting evidence .Ongoing RCTs specifically for oligometastatic esophageal cancer will hopefully shed further light on this subject (RENAISSANCE, NCT03161522) . The management of oligometastatic esophageal cancer is dependent on center of practice. A comprehensive discussion on this subject is beyond the scope of the module; however, relevant features include:
- Patient’s age, health, performance status
- Number and volume of metastases
- Location of metastases (para-aortic nodes, lung, liver are some potential candidates considered more amenable to surgery)
- Timeline: metachronous versus synchronous
- Basis of diagnosis
- Primary tumor status (controlled versus uncontrolled)
- T and N stage
- Local expertise and resources
Local Palliative Treatment
Dysphagia and esophageal obstruction are the most common complications of esophageal cancer. Obstruction should be considered as a potential cause for persistent nausea and vomiting. A grading scale is useful to communicate the severity of dysphagia :
- Grade 0: Able to tolerate normal diet without special care.
- Grade 1: Requires thoroughly-chewed food cut to fragments < 18mm in diameter.
- Grade 2: Able to swallow only semi-solid food.
- Grade 3: Liquid diet only.
- Grade 4: Unable to swallow liquids or saliva.
Numerous options are available for the management of severe dysphagia, including stenting (most commonly used), radiation therapy including EBRT and brachytherapy (also commonly used), endoscopic dilation, chemotherapy, and photodynamic therapy. Multimodal treatment is also reasonable . Palliative esophagectomy is generally discouraged due to high morbidity and mortality, especially in view of the poor prognosis of these patients .